Liquid handling robot for well plates

ABSTRACT

A liquid handling robot for handling well plates. The robot has a powered anvil which loads pipette tips from a tray onto the cones of a liquid handling head by first clamping the liquid handling head to the anvil and then ramming a movable plate carrying the pipette tips onto the cones. The robot also allows for fully automated swapping between different heads, such as liquid handling heads or pin heads. A head parking station is provided for parking heads when they are not being used. The robot has an automated pipette tip tray dispenser based on storage cassettes that store vertically stacked pipette tip trays. The trays are dispensed one at a time out of the storage cassette past retaining catches which are normally inwardly positioned to carry the pipette tip trays, but are outwardly biasable by a dispensing mechanism to allow the lowest tray in the shaft to pass onto a conveyor which moves the tray to a pick-up position from which the head can move the tray to the powered anvil for pipette tip loading onto a liquid handling head.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application is a Divisional of U.S. application Ser. No.10/144,763, filed May 15, 2002, incorporated herein by reference in itsentirety.

BACKGROUND OF THE INVENTION

The invention relates to liquid handling robots for well plates whichare used in biochemistry and microbiology for processing large numbersof samples in parallel.

FIG. 1 is a perspective view of a liquid handling robot according to theprior art. The robot comprises a movable head 10 that is used for liquidhandling and also has a mechanical manipulation capability. The head 10is movable in three orthogonal axes, x, y and z, with respective motorpositioners 12, 14 and 16. Head motion is controlled by a computercontrol system (not shown) via a control unit 15. The head 10 may alsoincorporates a camera (not shown) used to perform machine visionfunctions, such as bar code reading of well plates. The head 10 ismovable over a main bed 18 of the apparatus on which well plates andother biological sample containers, such as Q-trays, petri dishes andomni-trays, can be arranged, usually within an experimental area 19. Awaste chute 20 is incorporated in the main bed 18 and is flanked bystripping arm posts 21, the purpose of which is described below.

For mechanical manipulation, the head 10 is provided with pincers 25which are used to grip pipette tip trays. Using the pincers 25 and thepositioners 12, 14 and 16, the head 10 can be used to move pipette tiptrays around the apparatus as required. The head 10 is also providedwith jaws 26 arranged in the horizontal plane for gripping well platesor other sample plates such as omni-trays Q-trays or petri dishes.

FIG. 2 is a perspective view of a pipette tip tray 34 loaded withpipette tips 22. The pipette tips 22 are loaded into trays to allowrobotic handling. Each tray is a flat piece of stiff material, such asmetal or plastic, with an array of through holes in a grid conforming tothe desired well plate standard grid, the through holes having adiameter equal to part of the tapered neck portion of the pipette tips22, so that pipette tips 22 seat in the through holes.

For liquid handling, the head is provided with an array of pipette tipreceiving cones 24 with the array being conformant to the well platetype being processed, for example a 12×8 array for 96-well well plates.

FIG. 3 shows a single pipette tip cone 24 together with an upper end ofa pipette tip 22. Each cone 24 has a central capillary leading to areservoir formed by a barrel and piston, in which the piston is slidableup and down in the barrel to provide a syringing action. The outersurfaces of the cones 24 are corrugated to assist pipette gripping. Thecones are made of resilient material to aid formation of a liquid tightseal between themselves and the pipette tips 22 they are designed toreceive.

Referring back to FIG. 1, arranged on the main bed 18 of the apparatusthere can be seen a pipette tip tray anvil 32. The anvil 32 is a platewith an array of through holes in a grid conforming to one of the wellplate standard grids, the through holes having a diameter slightlylarger than the outer diameter of the widest part of the pipette tips22.

A number of trays 34 loaded with unused pipette tips 22 are held in ashelved storage rack 36, sometimes referred to as a “hotel” in the art,with each tray arranged on one shelf and vertically adjacent shelvesspaced far enough apart to avoid the pipette tips fouling each otherwhen they are slid in and out of the shelves. In the schematic drawing,the hotel is illustrated as having three racks, each with three shelves.A greater number of shelves would usually be provided in practice.

The action of loading pipette tips 22 onto the liquid handling head 10is now described. The head 10 is moved over to the pipette tip traystorage rack 36 and, using the pincers 25, one of the pipette tip trays34 is taken out and placed on the anvil 32. The head 10 is then moved sothat the array of cones 24 is aligned above the array of pipette tips22. Using the lead screw motor drive of the z-positioner 16, the head 10is then driven down so that the (male) cones 24 mate with the (female)upper apertures of the pipette tips 22, the anvil 32 acting as anabutment surface to allow the pipette tips 22 to be pushed onto thecones 24. The head 10 is then raised away from the anvil 32 using thez-positioner 16 with each of the cones 24 now loaded with a pipette tip22 ready for liquid handling.

Once the desired pipetting action has been completed, the pipette tips,which are disposable items, can be removed from the head as nowdescribed. The head 10 includes a slotted plate (not shown), immediatelyabove the cones 24 with the slots having a width greater than themaximum outer diameter of the cones and less than the maximum outerdiameter of the pipette tips 22. The slotted plate is hinged to the mainbody of the liquid handling head 10. The hinging action allows ejectionof pipette tips 22 from the cones 24 on which they are seated. Thehinged slotted plate is actuated by a lever acting on the slotted platebeing pushed onto the stripping posts 21 as the head 10 is driven downover the waste chute 20. The pipette tips are thus stripped off over thewaste chute 20.

Some undesirable aspects of this design have been identified.

The anvil-based pipette tip loading process is not always reliable. Theloaded pipette tips can on occasion fall off their cones, especiallyduring syringing out of the liquid reservoir. If this happens, theresultant spillage can destroy the integrity of a whole well plate,which may contain valuable reagents and contain samples obtained fromseveral processing steps already performed.

Manual loading of the pipette tip trays into the shelved storage rack isa fiddly, time consuming exercise, which needs to be performed with carein view of the fact that the pipette tips may be fragile and are heldloose in their trays.

The liquid handling robot is not capable of performing other actions,such as gridding or picking, which necessitates transfer of the wellplates to another machine if these actions need to be performed beforeor after the liquid handling actions. Each such transfer, carries acontamination risk, and is also inconvenient.

SUMMARY OF THE INVENTION Powered Anvil

According to the invention there is provided an anvil apparatus for aliquid handling robot comprising: an apertured plate for receiving anarray of pipette tips; a clamping arrangement for holding down a liquidhandling head of the liquid handling robot above the apertured plate;and a drive for forcing the apertured plate and the liquid handling headtogether while the liquid handling head is held down by the clampingarrangement in order to push pipette tips onto the liquid handling head.

The powered anvil of the invention is found to provide enhancedreliability, which is attributed to the fact that a controlled smoothaction can be provided for pressing the pipette tips onto the liquidhandling head. Moreover, by first clamping the liquid handling head tothe anvil, a well defined driving force can be applied with a separatedrive so that the driving force can be optimized for the pipette fittingaction.

This contrasts with the prior art approach of using the head's ownvertical motor drive to force the head down onto the pipette tips. Theprior art approach is believed to cause difficulties, since the motordrive of the liquid handling head is principally designed as apositioning device, and is not suited to being used effectively as a ramwhich may even damage the motor drive and compromise its linearity. Thevertical positioner's motor is neither designed to be driven against animmovable object, nor to deliver a controlled reproducible ramming forcewhen it is driven against an immovable object. In particular, it isbelieved that it is important to apply the force exactly in line withthe cones, i.e. perpendicular to the anvil plate surface, for reliablepipette tip loading, and this is not ensured by using the head'svertical positioner drive, since its drive axis is laterally offset fromcone array, so a slight hinging, bending or skewing effect may beoccurring at the instant of tip loading.

The drive may comprise a jack arranged to push the apertured plateupwards from below. The jack can be implemented with a pneumaticallyactuated piston assembly. Many other solutions could also be adopted,for example based on motor drives.

The clamping arrangement may comprise movable arms that are actuatablebetween clamping and free positions to clamp and release the liquidhandling head.

The array may conveniently conform to a well plate standard spacing, forexample for a well plate having 96 wells or 384 wells. In this regard,it is to be understood that the pipette tip array need not be as largeas a whole well plate array. For example, the pipette tip array may be a4×6 array, covering a quarter of a 96-well well plate which is made upof an 8×12 array of wells.

According to the invention there is further provided a liquid handlingrobot comprising: an anvil apparatus according to the first aspect ofthe invention; and a liquid handling head having an array of cones forreceiving pipette tips shaped to mate with the clamping arrangement ofthe anvil apparatus.

Pipette Tip Tray Dispenser

According to the invention there is provided a storage cassette forloaded pipette tip trays comprising: a storage shaft having an internalcross-section shaped and dimensioned to receive vertically stackedpipette tip trays loaded with pipette tips and to allow the pipette tiptrays to slide up and down the storage shaft; and a tray retainingmechanism having a retention position in which a lowest one of thepipette tip trays, and thus pipette tip trays vertically stacked aboveit, are retained in the storage cassette, and a release position inwhich the pipette tip trays are free to slide down the storage shaftpast the tray retaining mechanism.

The tray retaining mechanism may include spring biasing which can beurged into the release position by an actuating force, but otherwiseadopts the retention position. Alternatively, a variety of other movableretaining mechanisms could be used. For example, sliding catchesdrivable by motors between the two positions.

According to the invention there is further provided a pipette tip traydispenser comprising: a storage cassette according to the invention; anda base unit on which the storage cassette is mountable, the base unitcomprising a vertically movable pipette tip tray carrier that can beraised to support the lowest pipette tip tray held in the storagecassette and lowered to carry the lowest pipette tip tray out of thestorage shaft beyond the tray retaining mechanism.

The carrier is preferably arranged so that its upward motion to supportthe lowest pipette tip tray held in the storage cassette moves the trayretaining mechanism from its retention position to its release positionand its downward motion allows passage of the lowest pipette tip traybeyond the tray retaining mechanism before the tray retaining mechanismreturns to its retention position, thereby allowing the lowest pipettetip tray to be dispensed.

The carrier may advantageously lower the dispensed lowest pipette tiptray onto a conveyor for moving the pipette tip tray away from thestorage cassette for subsequent use.

In an embodiment of the invention, the storage cassette is detachablyarranged on the base unit.

It is noted that a strength of the pipette tip tray dispenser andstorage cassette design is that the dispensing channels and storagecassettes can be used for different pipette tip sizes without anyredesign. For example, if two dispensing channels are provided, one canbe used with a storage cassette loaded with large volume pipette tipsand the other with a storage cassette loaded with small volume pipettetips. A storage cassette loaded with small volume pipette tips installedin one dispensing channel could be swapped with a storage cassetteloaded with large volume pipette tips without any reconfiguration of themechanical components being necessary. The robot control system wouldhowever need to be informed.

According to the invention there is further provided a liquid handlingrobot comprising a pipette tip tray dispenser according to theinvention. The liquid handling robot may further comprise a head with amanipulator for removing pipette tip trays from the pipette tip traydispenser.

Automated Head Attachment

According to the invention there is provided a robot for handlingbiological sample containers, comprising: a head for carrying outprocesses on biological sample containers; a positioning apparatus formoving the head around the robot; and a parking station for parking thehead, wherein the head is connected to the positioning apparatus by anattachment mechanism drivable between a clamped state, in which the headis secured to the positioning apparatus, and a released state, in whichthe head can be detached from the positioning apparatus and deposited inthe park station.

The park station preferably comprises a plurality of parking bays, eachfor parking one head. This allows different types of head to be storedready for action, and also spare heads of the same type in case the headbeing used suffers a failure.

The robot will typically be provided with multiple heads, for exampletwo or more liquid handling heads, a mixture of liquid handling and pinheads, or two or more pin heads, thereby providing a flexiblemulti-purpose robot, capable of carrying out a variety of liquidhandling, spotting, gridding and colony picking tasks.

In an embodiment of the invention, the attachment mechanism comprises apiston assembly arranged to actuate a knee joint connected to a latch,the knee joint adopting a bent position in the released state andstraightened position in the clamped state. The piston assembly mayadvantageously include two piston cylinder units arranged in apush-me-pull-you configuration either side of the knee joint.

The attachment mechanism may include a communication feed-through, andeach head resident logic that allows the robot through the communicationfeed-through to receive identification data from any head that isattached to the positioning apparatus.

Liquid Handling Robot Combining at Least Two of the Powered Anvil,Pipette Tip Tray Dispenser and Automated Head Attachment

It will be understood that the powered anvil, pipette tip tray dispenserand automated head attachment can be advantageously combined in a singleliquid handling robot. In particular the combination of automatedpipette tip tray dispenser and powered anvil is a powerful combinationwhich allows for rapid and reliable liquid handling of well plates usingdisposable pipette tips. Liquid handling is further enhanced by theability to swap between multiple liquid handling heads in a fullyautomated fashion, the heads being specialized to perform differenttasks. For example, different liquid handling heads may be provided forlarge and small volume pipette tips, and the pipette tip tray dispensercan be loaded with two storage cassettes, one carrying large volumepipette tips and the other low volume pipette tips which are thenindependently dispensable through separate dispensing channels. Inaddition, the ability to be able to integrate picking or griddingfunctions within the liquid handling processes that is made possible bythe automated head swapping capability opens up a whole range of newapplications possibilities which would hitherto have necessitated usingdifferent robots and moving samples manually between them.

The various possible combinations of any two of the powered anvil,pipette tip tray dispenser and automated head attachment, or thecombination of all three, thus provide new and powerful functionalitiesadditional to the independent functionalities of each item.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the invention and to show how the same maybe carried into effect reference is now made by way of example to theaccompanying drawings in which:

FIG. 1 is a perspective view of a liquid handling robot according to theprior art;

FIG. 2 shows a pipette tip tray loaded with pipette tips;

FIG. 3 shows a pipette tip cone and upper end of a pipette tip;

FIG. 4 is a perspective view of a liquid handling robot according to anembodiment of the invention comprising an automated pipette tip traydispenser, powered anvil, and automated head swapping components;

FIG. 5 is a perspective view of the powered anvil;

FIG. 6 is a perspective view of a liquid handling head for pipetting upto 250 ml per pipette;

FIG. 7 is a perspective view of a pipette tip tray loaded with pipettetips;

FIG. 8 is a further perspective view of the liquid handling head from adifferent perspective than FIG. 6 showing the underside of the liquidhandling head;

FIG. 9 is a perspective view of the pipette tip tray dispenser;

FIG. 10 is an end view of the pipette tip tray dispenser;

FIG. 11 is a side view of the pipette tip tray dispenser;

FIG. 12 is a plan view of the pipette tip tray dispenser;

FIG. 13 is a close-up side view of a storage cassette loaded withpipette tip trays;

FIG. 14 is a view from below of a storage cassette loaded with pipettetip trays;

FIGS. 15A-D are schematic end views showing four steps in dispensing apipette tip tray from a storage cassette;

FIG. 16 is a side view of a storage cassette loading bay;

FIG. 17 is a side view of the head latching unit that is attached to thez-positioner motor drive;

FIG. 18 is an exploded perspective view of the head latching mechanismof the head latching unit;

FIG. 19 is an exploded perspective view of the head latching unit withthe head latching mechanism of FIG. 18 partly assembled;

FIG. 20 is a perspective view of a liquid handling head showing partsused to secure the head to the head securing unit; and

FIG. 21 shows the head attached to the head securing unit.

DETAILED DESCRIPTION Machine Overview

FIG. 4 is a perspective view of a liquid handling robot according to anembodiment of the invention. The robot comprises a movable head 110 thatis used for liquid handling and also has a mechanical manipulationcapability. The head 110 is movable in three orthogonal axes, x, y andz, with respective motor positioners 112, 114 and 116. Head motion iscontrolled by a computer control system (not shown). The head 110 mayalso incorporates a camera (not shown) used to perform machine visionfunctions, such as bar code reading of well plates. The head 110 ismovable over a main bed 118 of the apparatus on which well plates andother biological sample containers, such as Q-trays, petri dishes andomni-trays, can be arranged as well as other items such as vacuummanifolds 102 and shakers 104 for processing well plates. Adjacent tothe vacuum manifolds 102 and shakers 104 there is a general processingarea 105 where well plates, liquid reservoirs and other containers canbe arranged for conducting experiments. The main bed of the apparatus issupported at a convenient height on a table frame 106. A waste chute 120is incorporated in the main bed 118 and is flanked by stripping armposts (not visible). Situated on the far side of the main bed 118 thereis a well plate storage rack 108 with four shelf stacks arranged side byside. A slidable cover for the well plate storage rack is alsoillustrated. Well plates can be taken out of the storage rack 108 by thehead 110 using gripping jaws (not visible).

The robot has a powered pipette tip tray anvil 130 which is described indetail further below with reference to FIGS. 5 to 8.

The robot also has an automated pipette tip tray dispenser 160 which isdesigned to accommodate two pipette tip tray storage cassettes 170, onefor large volume pipette tips (for pipetting up to 250 microliter) andone for small volume pipette tips (for pipetting up to 50 microliter).Only one fitted storage cassette 170 is illustrated. The storagecassettes 170 can be installed and removed from the dispenser 160 byhand. The automated pipette tip tray dispenser 160 and the storagecassettes 170 are described in detail further below with reference toFIGS. 9 to 16.

The robot has the capability of automatically changing between differentheads. The available heads for the particular robot configuration can beparked in bays 210 within a park station 200. Two parking bays 210 areshown in the illustrated park station 200. These are for two differentliquid handling heads, a large volume item (up to 250 microliters perpipette) and a small volume item (1-50 microliters per pipette). Inother embodiments, three, four or more bays could be provided. As wellas liquid handling heads, pin heads for colony picking or spotting orgridding could be provided depending on the robot configuration that isdesired. The head swapping functionality and associated equipment isdescribed in detail further below with reference to FIGS. 17 to 19.

Powered Anvil

FIG. 5 is a perspective view of the powered anvil 130. The components ofthe anvil 130 are arranged on a mounting plate 131 which is bolted tothe underside of the main bed of the robot via mounting pillars 144, oneof which is shown. The anvil 130 comprises a top plate 135 which isperforated with an array of holes 141 having diameters large enough toloosely receive pipette tips and arranged in a standard well plate gridso as to receive pipette tips loaded into a pipette tip tray. Around themargin of the top plate, three tray clamps 139 are provided. These moveapart to a released position when a spigot 140, arranged to one side ofthe top plate 135 and extending above the plane of the top platesurface, is pushed down. A spring loaded mechanism connects the spigot140 to the tray clamps 139. In use, a pipette tip tray is loaded intothe anvil by lowering the liquid handling head, with a tray gripped inits pincers, down onto the top plate 135, where the head itselfdepresses the spigot 140 opening up the tray clamps 139 for acceptanceof the tray. The head is then raised allowing the spigot 140 to risewith it and thus the tray clamps 139 to move back inwards relative tothe top plate 135, thereby clamping the tray in place.

The top plate 135 is arranged spaced apart above a base plate 134, thetwo being slidably connected by vertically arranged posts 145, whereinthe top plate 135 can be slid up and down the posts 145. Movement of thetop plate 135 is driven by a pneumatic piston assembly comprising acylinder unit 132 and piston 133. The cylinder unit 132 is double actingdriven by two compressed air feed lines (not shown) and has two stablepositions, extended (as illustrated) and retracted. Actuation of thepiston 135 moves an elongate cam 142 along a rail 143. The cam 142 has aramp (not visible) which engages with the underside of the top plate 135to push it vertically upwards on the posts 145 when the piston 133 movesover a portion of its travel close to its extended position. Motion ofthe cam 142 also drives rotation of a pair of flippers 137 which act asclamping arms for a robot head. The flippers 137 are mounted on columns136 that are rotatably mounted in the mounting plate 131. At their lowerends, the columns 136 are connected to inwardly directed lever arms 138that are in engagement with a waisted portion of the elongate cam 142.Motion of the elongate cam 142 along a portion of the piston's travel,that is closer to the retracted position than the first-mentionedportion of travel, engages one end of the cam's waisted portion with thelever arms 138 to move the latter, thereby rotating the columns 136 andmoving the flippers 137.

It will thus be understood that motion of the piston from its retractedposition to its extended position initially causes the flippers 137 tomove around from an alignment generally parallel to the piston motiondirection, to an inwardly pointing alignment as illustrated in FIG. 5,and subsequently causes the top plate 135 to be driven upwards. Thesignificance of these movements is be discussed further below.

Finally in respect of FIG. 5, it is noted that the anvil apparatus 130is arranged in the robot as illustrated in FIG. 4, with the pistonassembly 132, 133 and base plate 134 below the level of the main bedsurface. As already mentioned, this is achieved by bolting the anvilapparatus to the underside of the main bed of the robot via the mountingpillars 144.

FIGS. 6 and 8 are perspective views from different angles of a liquidhandling head 110 for pipetting up to 250 ml per pipette. The head 110includes clamping slots 148 arranged to receive the flippers 137 whenthe head is lowered onto the anvil with a loaded pipette tip trayalready in the anvil, and when the flippers 137 are then rotated intothe position illustrated in FIG. 5 by motion of the cam. In use, fittingpipette tips onto the head proceeds as follows.

1. A pipette tip tray loaded with pipette tips is placed onto the anviltop plate 135 in the manner described further above.

2. The head is lowered down onto the anvil top plate 135 with the cones124 aligned with the pipette tips 122 and loosely fitted therein.

3. The piston assembly 132, 133 is actuated with compressed air to drivethe piston 133 from its retracted position to its extended positionwhich first rotates the flippers 137 into the clamping slots 148 to holddown the head, and second jacks the anvil top plate 135 upwards to ramthe upper ends of the pipette tips 122 into the 124 cones.

Here it will be understood that the clamping action of the flippers 137serves to provide an abutment preventing upward motion of the head 110in response to the upward driving force of the top plate 135 imparted bythe ramped cam 142. In this way, the pipette tips 122 can be fitted tothe cones 124 with a controlled force acting in a controlled direction,which provides for highly reliable liquid tight pipette tip attachmentto the cones.

Other parts of the head 110 are now described.

The head 110 is provided with pincers 125 which are used to grip pipettetip trays. The pincers 125 are driven by a motor drive 151. Using thepincers 125 and the robot's x-, y- and z-positioners, the head 110 canbe used to move pipette tip trays around the apparatus as required. Thehead 110 is also provided with jaws (not shown) for gripping well platesor other sample plates such as omni-trays Q-trays or petri dishes. Thejaws are arranged on the opposite side of the head 110 to the pincers125.

The head 110 is provided with an array of pipette tip receiving cones124, one of which is illustrated in FIG. 8. The cones 124 are arrangedin an array that is conformant to the well plate type being processed,which in this example is a 12×8 array for 96-well well plates. A singlepipette tip 122 is also shown in FIG. 8 for illustration purposes.

Each cone 124 is as illustrated in FIG. 3 with a central capillaryleading to a reservoir formed by a barrel and piston, in which thepiston is slidable up and down in the barrel to provide a syringingaction. The reservoirs are located in the interior of the main body 155of the head 110. The outer surfaces of the cones 124 are corrugated toassist pipette gripping. The cones 124 are made of resilient material toaid formation of a liquid tight seal between themselves and the pipettetips 122. The head 110 is secured to the z-positioner via a securingplate 149 on its upper side. The securing plate 149 also provides a hostfor an electrical contact pad 150 which mates with a correspondingcontact pad on the z-positioner. The contact pad 150 provides the head110 with electrical power feeds for driving the pincer motors, syringingpistons and other functions and also communication feed-throughs forproviding communication lines from the main robot to the resident logic300 within the head. For example each head has a unique identifier sothat the robot can interrogate the head to receive identification dataand thus determine the head's identity, which will not only define thehead's handling while installed, but also define its parking bay whenthe heads need to be exchanged or parked.

The bottom side of the head 110 has a slotted plate 146 mounted byhinges 153, with the slots 152 being evident in FIG. 8. The slot widthis greater than the maximum outer diameter of the cones 124, but lessthan the maximum outer diameter of the pipette tips 122. Pipette tips122 can be stripped from the cones 124, and thus the head 110, byhinging the slotted plate 146. The slotted plate 146 is actuated by astripping arm 147 which is mounted on a pivot 154 and has one end thatprotrudes beyond the side of the main body of the head and another endthat is situated above an edge flange of the slotted plate 146. In use,the protruding end of the stripping arm is actuated when the head 110 ismoved down over the waste chute 120 and encounters a stripping post,which pivots the stripping arm so that its other end pushes down on theflange of the slotted plate 146 causing hinging of the slotted plate.The pipette tips 22 are thus stripped off over the waste chute 120.

FIG. 7 is a perspective view of a pipette tip tray 156 loaded withpipette tips 122. (FIG. 7 is the same as FIG. 2, but is reproduced toillustrate a pipette tip tray juxtaposed with a liquid handling headembodying the invention.) The pipette tips 122 are loaded into trays toallow robotic handling. Each tray is a flat piece of stiff material,such as metal or plastic, with an array of through holes in a gridconforming to the desired well plate standard grid, the through holeshaving a diameter equal to part of the tapered neck portion of thepipette tips 122, so that pipette tips 122 seat in the through holes.

Pipette Tip Tray Dispenser

FIGS. 9 to 12 show views of the pipette tip tray dispenser 160 inperspective, from the end, from the side and from above respectively.

FIG. 13 is a detail side view of the lower end of a storage cassette 170loaded with a stack of pipette tip trays 156 loaded with pipette tips122.

FIG. 14 is a view from below of a storage cassette 170.

The pipette tip tray dispenser 160 is designed to accommodate twopipette tip tray storage cassettes 170, one for large volume pipettetips (for pipetting up to 250 microliter) and one for small volumepipette tips (for pipetting up to 50 microliter). Only one storagecassette 170 is illustrated in order to reveal details of the otherstorage cassette docking area. The top level of loaded pipette tips 122carried on a tray 156 within the cassette is also shown.

Each storage cassette 170 is provided with a carrying handle 173 forease of installation into and removal from the dispenser 160. Thestorage cassettes 170 stand sleeved in the upper part of the dispenser160 without locking or latching. The interior of each storage cassette170 forms a storage shaft 172 having an internal cross-section shapedand dimensioned to receive vertically stacked pipette tip trays loadedwith pipette tips. The vertical stacking is such that each pipette tiptray above the lowest one is supported by the upper ends, i.e. the toprim surface, of the pipette tips loaded into the pipette tip trayimmediately below. In this stacking position, the lower ends of thepipette tips from each tray (apart from the lowest one) extend into theupper apertures of the pipette tips carried by the tray immediatelybelow. The storage shaft 172 is smooth in the vertical direction toallow the pipette tip trays to slide up and down. The lowest stackedpipette tip tray, and thus any other pipette tip trays stackedvertically above it, are retained in the storage shaft 172 by two pairsof mutually facing spring catches 171 which normally adopt a trayretention position, but can be forced outwards to a tray releaseposition in which pipette tip trays are able to slide down the storageshaft past the catches 171. Tray dispensing is described in more detailfurther below, after a fuller description of the dispenser 160 has beengiven.

The dispenser components are mounted to a main plate 161 which bolts tothe top surface of the robot main bed 118. A housing 188 formed of twoend plates, two side plates and a dividing plate between the side platesis arranged on the upper side of the main plate 161 and defines twogenerally rectangular apertures for receiving the storage cassettes 170from above. Two tray dispensing channels are formed by the side platesand dividing plate which are spaced apart by slightly less than the traywidth. Trays can be slid along the dispensing channels located inmutually facing L-section ledges 186 machined into the upper, inwardlyfacing corners of the side and dividing plates. A tray located in theledges 186 is visible in the left-hand dispensing channel of FIG. 12.Trays are driven along the dispensing channels away from the storagecassette docking area by a conveyor arrangement comprising a fixed base184 and linearly movable slider 185 which has a dog 187 standing up nearthe rear end of the slider high enough to push a tray along thedispensing channel that is seated in the L-section ledges. When theslider 185 is fully retracted (as in FIG. 9 for example), the dog 187 ispositioned sufficiently close to the rear end of the slider so that itdoes not foul a tray being dispensed from the storage cassette 170.

The conveyor drive components are obscured in the perspective view fromabove of FIG. 9, since they lie below the main plate 161, but arevisible in the end and side views of FIGS. 10 and 11. The two sliders185 can be moved back and forth in unison by a belt drive comprising twobelts 181 which are driven from a common electric motor 180 through asuccession of toothed gear wheels 182, 183. (If desired, independentconveyor drives could be provided.) Considering one dispensing channel,driving the belt drive in one direction (clockwise in FIG. 11) willcause the dog 187 to push a tray out of the storage cassette dockingarea to the head pick-up area (tray movement to the right in FIG. 11).Once the dog 187 has reached its end position, the drive direction isreversed (to counterclockwise in FIG. 11), and the dog 187 moves back tothe position shown in FIG. 9 ready for pushing another tray along thedispensing channel.

Also arranged on the underside of the main plate 161 are components fordriving two pairs of sliding blades 165 that actuate the spring catches171 of storage cassettes 170 sleeved in the housing 188. The slidingblades 165 are most clearly seen in FIGS. 10, 11 and 12. The slidingblade pairs 165 are spaced apart by a distance slightly less than thetray width. The interior of the lower ends of the storage cassettes isprovided with side recesses 174 which allow space for the blades 165 tobe moved up into the lower end of the storage cassette sufficiently highto outwardly displace the spring catches 171 and abut the lowest trayheld in the storage cassette 170. The side recesses 174 into which theblades can be moved are most clearly evident in FIG. 14 which is a viewfrom below of a storage cassette 170. FIG. 14 also shows corner recesses175 in the inside of the cassette which are provided to avoid trayjamming.

The actuation mechanism for raising and lowering the blade pairs 165 isnow described. The blades of each pair are rigidly connected to eachother by a rod 167. Each rod 167 is connected to a piston 166 arrangedin a cylinder 162. The piston and cylinder pairs form pneumatic pistonassemblies that are driven by compressed air lines (not shown) betweenan extended (upper) position and a retracted (lower) position. In theretracted position (the one illustrated), the upper edges of the blades165 lie slightly below the level of the horizontal part of the L-sectionledges 186. In the extended position, the upper edges of the blades 165lie slightly above the level of the lower surface of a tray 156supported on the spring catches 171. The pneumatic cylinders 162 arebolted hanging down from a cylinder mounting plate 163 which is in turnsuspended below the main plate 161 by pillars 164.

FIGS. 15A-D are highly schematic end views showing four steps indispensing a pipette tip tray from the storage cassette. These areschematic versions of the same view as FIG. 10. To highlight theprinciples of operation, only the spring catches are shown together witha number of vertically stacked trays filled with pipette tips and ablade pair.

FIG. 15A shows the starting position with a number of filled trays (sixin the figure) loaded in the storage cassette, the lowest tray restingon the horizontal surfaces of the spring catches which thereby supportthe tray stack. The blade pair is in its lowest position with itsdriving piston retracted.

FIG. 15B shows a subsequent position in which the blade pair has beenslid to its uppermost position, with the driving piston extended. Inthis position, the blades have laterally displaced the spring catches soas to be in contact with the edges of the lowest tray and therebysupport the tray stack.

FIG. 15C shows a subsequent position in which the blade pair has beenpartially withdrawn taking the lowest tray with it. As the blade pairlowers from the uppermost position as shown in FIG. 15B, the springcatches move back into position, but only after the lowest tray hasmoved past them, thereby catching the next tray as illustrated and thussupporting the remainder of the tray stack.

FIG. 15D shows a subsequent position in which the blade pair is in itslowest position with its upper edges no longer in contact with thedispensed tray which is now resting in the dispensing channel on theL-shaped ledges which are schematically indicated ready for dispensingvia the conveyor. After dispensing the tray, the apparatus has returnedto the state of FIG. 15A.

FIG. 16 is a side view of a storage cassette loading bay. The loadingbay has a solid metal base 190 sufficiently heavy to provide stabilityon which four legs 192 stand in a rectangular arrangement. The legs 192support a top 193 perforated with holes that match the holes in thepipette tip trays for which the loading bay is intended. A stack ofpipette tip trays 156 with pipette tips 122 can be arranged on the top193, a stack of four being shown in the figure. A stack of pipette tiptrays can be conveniently inserted into an empty storage cassette bylifting the storage cassette over the loading bay, for example using itshandle, and then lowering the storage cassette down onto the loading bayso that the trays push past the spring catches and into the storageshaft. The loading bay legs 192 have a length suitable for the loading,so that when the bottom of the storage cassette rests on the base 190,the plane of the loading bay top 193 is slightly above the plane of thehorizontally extending part of the spring catches on which the lowesttray would normally bear.

Automated Head Changing

FIG. 17 is a side view of the head latching unit 220 that is attached tothe z-positioner motor drive and serves to allow different heads to beloaded and unloaded.

FIG. 18 is an exploded perspective view of the head latching mechanismof the head latching unit 220.

FIG. 19 is an exploded perspective view of the head latching unit 220with the head latching mechanism of FIG. 18 partly assembled.

The head latching unit 220 comprises a housing made of top and bottomplates 243 and 240 and left and right end plates 242 and 241.Non-structural side plates 244 are also provided (omitted from FIG. 17,but evident in FIG. 19). The bottom plate 240 is provided on its lowerside with locating stubs 227 to assist location of the head latchingunit in corresponding holes in the heads.

The latching mechanism is driven by a push-me-pull-you pneumatic pistonassembly comprising a delatch driving piston 250 and a latch drivingpiston 260 with respective cylinders 226 and 266. The cylinders 226 and266 are rotatably mounted by spigots 252 (see FIG. 18) located in blocks245 (see FIG. 19) secured to the base plate 240 in a manner similar to ahowitzer.

The cylinders act on a knee joint 255 connecting to a floating upperjoint 257 by an upper link 247. The knee joint 255 is also connected toa lower fixed joint 256 by a lower link 248. The fixed joint 256 islocated in the side plates 246 (only one of which is shown in FIG. 18)by a locating pin. The knee joint 255 is connected to both pistons 250,260 by respective connectors 251 assisted by a locating pin 253. Theknee joint 255 has a pin 253 running through it which fits into a pairof arcuate slots 223 in the side plates 246 retained by a pair ofoutside circlips 254. The floating upper joint 257 also has a pin 253running through it which fits in a pair of vertical slots 225 in theside plates 246 retained by a pair of outside circlips 254. The floatingupper joint pin also pivotally mounts a latching arm 222. The latchingarm 222 extends obliquely down to a non-jointed bend 258 with a holethrough which a further pin 253 passes which is retained by outsidecirclips 254 and fits into an L-shaped slot 224 in the side plates 246.After the non-jointed bend 258, the latching arm 22 extends verticallydown and then at right angles thereto extends further to form a latchsupport which bears a latch 221.

Before describing the latching action by which heads are attached to anddetached from the latching unit 220, the latching parts of the heads arefirst described.

FIG. 20 is a perspective view of a liquid handling head 110 showingparts used to secure the head to the head securing unit. Forcompleteness, it is noted that the liquid handling head illustrated isone for pipetting volumes of 1-50 microliters per pipette, in contrastto the larger volume pipetting provided by the liquid handling headillustrated in FIGS. 6 and 8. The latching components of all heads willbe similar.

Parts familiar from the description of FIGS. 6 and 8 will be recognized,and not further described. These are the tray pincers 125, pincer motordrive 151, securing plate 149 and contact pad 150. Locating holes 233for accepting the locating stubs 227 on the head latching unit 220 canbe seen. In addition there are four locating stubs 232 on the head 110which locate in corresponding holes in the head latching unit 220 (notvisible in FIGS. 17-19). The stubs 232 are mounted on a plate 231 whichmounts a lower latch 230 which has a fixed position and is shaped anddimensioned to engage with the latch 221 of the head latching unit.

Although not relevant for the latching, it is noted that FIG. 20 alsoshows upper and lower subassemblies 235 and 234 respectively. The lowersubassembly 234 has ramps 236 on its upper surface on which ride wheels237 that are carried by the upper subassembly 235. Riding up and downthe ramps changes the separation between the subassemblies 235 and 234and is the movement that provides the syringing action, the reservoirpistons being carried by the upper subassembly 235 and the reservoircylinders being part of the lower subassembly 234. The motion is drivenby an electric motor carried in the head.

Returning to the latching mechanism, this has two basic positions, alatched position, in which the head is gripped by the latch and securelyengaged with the head latching unit 220, and a delatched pre-engagementposition. FIGS. 17-19 illustrate the mechanism in the latched position.In view of this, movement of the mechanism from the latched position tothe delatched position is described. This is the movement that would beperformed when a head had been returned to its parking bay and was to bereleased by the head latching unit to allow the z-positioner with headlatching unit to be moved away to pick up a different head.

Referring to FIG. 17, the delatching piston 250 is pneumaticallyactuated by compressed air through a feed line (not shown) which pushesthe knee joint 255 to the right (as viewed in the figures) which pushesthe pin around the arcuate slot 223. This forces the floating upperjoint 257 vertically down guided and constrained by the vertical slot225. Initially, the non-jointed bend 258 is also forced vertically downguided by the upright part of the L-shaped slot 224. During this phaseof the delatching, the latch 221 is being moved vertically down,allowing it to become free of the head's latch 230 (assuming the head110 is supported in its parking bay). Once the downward motion proceedsto the point at which the base of the L-shaped slot has been reached bythe non-jointed bend 258 of the latching arm 222, the latching arm 222is forced to rotate by the pin through the non-jointed bend 258 beingconfined to move in the base of the L-shaped slot until it abuts the endof the base section of the L-shaped slot. The mechanism is now in thedelatched position, with the knee joint 255 at its maximum bend and thelatching arm 222 at is maximum swing angle away from vertical, swunginto a space 261 provided within the plate 231. At this point, thelatching arm 222 has swung away sufficiently to allow the latching unit220 to be lifted away from the head 110 by a simple vertical motion ofthe z-positioner. It will now be appreciated why the piston assembliesare pivotally mounted, namely to accommodate movement of the pins in theslots 223, 224 and 225.

Motion from the delatched to the latched position proceeds approximatelyin the reverse sequence. It is initiated by actuation of the latchingpiston 260 which acts on the knee joint 255 to straighten it out. Thereverse sequence of slot motion is performed in relation to thelatch-to-delatch motion with the latching arm 222 being forced to movevertically upward in the L-shaped slot 224 when the pin through thenon-jointed bend 258 reaches the corner of the L-shaped slot 224. Worthyof mention is the fact that it in the final stages of straightening whenmoving into the latched position, the design allows a high amount ofclamping force to be exerted, with the head's latch 230 being squeezedbetween the latching unit's latch 221 and the bottom of the lower link248. This feature provides a highly secure latching of the head.

FIG. 21 shows the low volume liquid handling head 110 attached to thehead securing unit 220 with the latching mechanism in the latchedposition described above.

It will be appreciated that although the automated head attachment anddetachment has been described in relation to a liquid handling head, itis universally applicable to any head, for example pin heads forgridding or colony picking, thereby allowing multiple functions to beperformed by a single robot.

1. A robot for handling biological sample containers, comprising: (a) ahead for carrying out processes on biological sample containers; (b) apositioning apparatus for moving the head around the robot; (c) anattachment mechanism; and (d) a parking station for parking the head,wherein the head: (i) is connected to the positioning apparatus by theattachment mechanism which is drivable between a clamped state, in whichthe head is secured to the positioning apparatus, and a released state,in which the head can be detached from the positioning apparatus anddeposited in the park station, and (ii) is configured with residentlogic comprising head identification data; wherein the attachmentmechanism includes a communication feed-through to transmit the headidentification data from the head to a computer control system, andwherein the communication feed-through comprises an electrical contactpad on the head which is connected to a corresponding contact pad on theattachment mechanism to allow transmission of identification data fromthe resident logic located in the head to the computer control system;and, wherein the parking station functions to house the head when thehead is not attached to the positioning apparatus.
 2. The robotaccording to claim 1, wherein the park station comprises a plurality ofparking bays, each for parking one head.
 3. The robot according to claim2, comprising a further head.
 4. The robot according to claim 3, whereinthe head and the further head are both liquid handling heads forpipetting.
 5. The robot according to claim 3, wherein the head is aliquid handling head and the further head is a pin head for pipetting,colony picking, spotting, gridding or any combination thereof.
 6. Therobot according to claim 3, wherein the head and the further head 30 areboth pin heads for pipetting, colony picking, spotting, gridding or anycombination thereof.
 7. The robot according to claim 1, wherein theattachment mechanism comprises a piston assembly arranged to actuate aknee joint connected to a latch, the knee joint adopting a bent positionin the released state mid straightened position in the clamped state. 8.The robot according to claim 7, wherein the piston assembly includes twopiston cylinder units arranged in a push-me-pull-you configurationeither side of the knee joint.
 9. The robot according to claim 1,wherein the contact pad further provides the head with electrical powerfeeds.
 10. A releasable head for a biological sample container handlingrobot, comprising: (a) a communication feed-through for communicating toa robot to which the head is attached, wherein the communicationfeed-through comprises an electrical contact pad which connects the headto the robot allowing transfer of head-identification data from the headto a computer control system; and (a) a resident logic component locatedin the head which allows communication of the head identification datato the computer control system through the communication feed-through toidentify the head attached to the robot.
 11. The head according to claim10, wherein the contact pad further provides the head with electricalpower feeds.
 12. The head according to claim 10, wherein the head is aliquid handling head for pipetting.
 13. The head according to claim 10,wherein the head is a pin head for pipetting, colony picking, spotting,gridding or any combination thereof.